Fig. 3.

Functional effects of deleting C-zone repeats of skeletal muscle and the heart. a In vivo force generation by the gastrocnemius muscle complex. The specific force frequency relation revealed significantly reduced force levels in Ttn ^ΔC1-2 mice (see inset). b, c Force–sarcomere length relations of skinned fiber bundles from EDL muscle activated by maximal calcium levels. b Specific force is significantly reduced in Ttn ^ΔC1-2 mice (red symbols) with a reduction that, relative to WT levels, increases with sarcomere length (inset). c Force normalized to maximal force at optimal length reveals a descending limb with a slope that is significantly steeper in Ttn ^ΔC1-2 mice (inset). Mice at 60 days of age were used (n = 6 male and 2 female WT; n = 7 male and 2 female Ttn ^ΔC1-2). d, e Pressure–volume (PV) analysis of the left ventricular chamber. Sample PV loops in Fig. 3d reveal reduced end-systolic pressures and a reduced slope of the end-systole PV relation (ESPVR) in Ttn ^ΔC1-2 mice (red), with summarized results in Fig. 3e. Male mice at 62–74 days of age were used (n = 7 WT and n = 8 Ttn ^ΔC1-2). f Echocardiography revealed wall thinning (diastolic wall thickness (WTd)), an increased eccentricity index, and a reduced ejection fraction (EF), all indicating that Ttn ^ΔC1-2 mice have dilated cardiomyopathy (DCM). The 50-day-old male mice were studied (n = 8 WT and n = 8 Ttn ^ΔC1-2). Mean values±s.e.m. are shown. Additional statistical analysis is provided in Supplementary Table 4 (** denotes p < 0.01; ***p < 0.001, and ****p < 0.0001)